Chk2-p53 and JNK in irradiation-induced cell death of hematopoietic progenitors and differentiated cells in Drosophila larval lymph gland

• Published in: Biology open Vol. 10; no. 8
• Main Authors: Nguyen, Tram Thi Ngoc, Shim, Jiwon, Song, Young-Han
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 15.08.2021; The Company of Biologists
• Subjects: Apoptosis; Blood cells; Cell cycle; Cell death; Cell differentiation; CHK2 protein; Deoxyribonucleic acid; DNA; DNA damage; dna damage response; Drosophila; Environmental changes; Fruit flies; Hematopoiesis; hematopoietic progenitor; Hemocytes; Hemopoiesis; Homeostasis; Insects; Ionizing radiation; Irradiation; Lymph; Lymph gland; Mortality; p53 Protein; Progenitor cells; Radiation damage; Senescence; Stem cells; Hematopoietic progenitor; Ionizing radiation; Cell death; DNA damage response; Hematopoiesis; Drosophila
• DOI: 10.1242/bio.058809
• ISSN: 2046-6390

Ionizing radiation (IR) induces DNA double-strand breaks that activate the DNA damage response (DDR), which leads to cell cycle arrest, senescence, or apoptotic cell death. Understanding the DDR of stem cells is critical to tissue homeostasis and the survival of the organism. Drosophila hematopoiesis serves as a model system for sensing stress and environmental changes; however, their response to DNA damage remains largely unexplored. The Drosophila lymph gland is the larval hematopoietic organ, where stem-like progenitors proliferate and differentiate into mature blood cells called hemocytes. We found that apoptotic cell death was induced in progenitors and hemocytes after 40 Gy irradiation, with progenitors showing more resistance to IR-induced cell death compared to hemocytes at a lower dose. Furthermore, we found that Drosophila ATM (tefu), Chk2 (lok), p53, and reaper were necessary for IR-induced cell death in the progenitors. Notably, IR-induced cell death in mature hemocytes required tefu, Drosophila JNK (bsk), and reaper, but not lok or p53. In summary, we found that DNA damage induces apoptotic cell death in the late third instar larval lymph gland and identified lok/p53-dependent and -independent cell death pathways in progenitors and mature hemocytes, respectively.